The present invention relates most generally to microsensors for sensing chemical or biological analytes, and, more particularly, the present invention is related to hybrid sensors capable of simultaneously measuring the thickness and conductivity change of a polymer film exposed to a particular chemical and/or biological analyte to sense the presence of particular chemical and/or biological analytes.
The construction of rugged, inexpensive, reliable and small chemical microsensors whose output can be expressed in terms of a measurable electrical signal such as DC conductivity is of current interest. The goal of current research and development is to construct devices that can detect and identify chemical or biological analytes alone or in a complex mixture. Ideally, such sensors should be able to function in either a liquid or vapor environment.
Fields where the demand is great are volatile gas detection for environmental studies, medicine, and counterterrorism. Sensing of organic vapors has been achieved by measuring changes in conductivity or thickness of organic thin films. Specifically, volatile airborne organics when spilled or accidentally released into the air can have harmful effects on the internal operations of instruments and living creatures. Early detection can minimize damage and expedite cleanup procedures.
Identification and quantification of airborne organics such as benzene, tetrahydrofuran, ethanol, chloroform, and others has been demonstrated by Freund and Lewis (Proceedings of the National Academy of Sciences, 92, 2652 (1995)) using a polypyrrole material based xe2x80x98organic nosexe2x80x99 sensing unit. The sensor was formed by depositing a polypyrrole thin film on a cross sectional cut of a capacitor. The cross section had parallel rows of metal to which leads were attached to. The conductive polymer bridged the gap between the metal, completing the previously open circuit. The polymer was sensitive to the exposed airborne gases, absorbing them into the thin film. An array of these sensing elements produced a chemically reversible and consistent pattern of electrical resistance changes upon exposure to different organic analyte vapor. These patterns were repeatable and unique for each analyte.
Medically, the ability to detect biogenic amines would aid doctors in the diagnosis of disease. For example, biogenic amines such as aniline and o-toluidine have been reported as biomarkers for lung cancer, while di and tri-methylamines have been reported as the cause of the fishy uremic breath observed by patients with renal failure. Early detection of these amine groups would expedite diagnosis and treatment of patients. This technology could also allow for remote diagnosis by doctors of patients living in areas without proper health care Polyaniline polymer doped with carbon black has yielded a class of chemiresistor detectors able to sense amine groups at a sensitivity 1 million fold greater than that of the human olfactory system (G. Sotzing, et al., Chem. Mater., 12, 593-595, (2000)). When an amine analyte such as butylamine is exposed to the film it causes a swelling in the polymer film. This swelling moves the conductive carbon atoms farther apart from each other within the film matrix. The film resistance increases due to the increased distance between the conductive carbon atoms. The resistance increase for the amine groups tested was unique and differentiable from the other responses.
Finally, in light of the emerging terrorism threat, the ability to detect nerve gases or other volatile/toxic gases in public buildings and transportation areas by reliable sensing equipment has become of increased importance. Polyethylene oxide polymer chemiresistors doped with lithium perchlorate have been shown to accurately detect and differentiate between the nerve gas simulants diisopropylmethylphosphonate (DIMP), dimethylformamide (DMMP), and dimethylmethylphosphonate (DMF) (R Hughes, et al., Journal of The Electrochemical Society, 148, 1-8, (2001)). In this system the polymer molecules rearrange during film swelling as the analyte is absorbed. The conductivity of the system increases because the mobile charge has more opened pathways to travel through The AC impedance of the system is reduced by a characteristic amount, producing a signature impedance change for each gas.
As early as 1986 the general principles behind chemiresistor detectors had been demonstrated. Early sensing experiments using metal ion doped phthalocyanine thin films spread on the surface of Interdigitated (IDA) electrodes showed resistance changes in the film when exposed to organic analyte vapor. These systems relied on the fact that the resistance for a given thin film depended upon the type of vapor (and its concentration) exposed to the sensor. Consistent resistance responses to gas exposure have been shown by organic polymer based systems doped with a conductive ion or plasticizer. Other materials such as clays have also been successfully used.
Organic polymer systems work through the process of analyte gases diffusing (dissolving or partitioning) into the matrix of the polymer film. This changes the conductivity of the polymer by swelling or contracting the film and changing either the distance between conductive atoms or the pathway taken by the mobile charge. The simplest systems use organic polymers that are naturally conductive such as polyacetylene Melanin. The conductivity of such systems can be enhanced through the addition of a plasticizer that acts as a dielectric material in the polymer matrix. This enhances the intermolecular capacitance just as a dielectric does in a parallel plate system. The polymers conductivity can also be increased through the addition of a doping agent such as a conductive salt or carbon black residue. These two materials increase the charge carrying ability of the polymer through different means. The addition of a conductive salt increases the number of mobile charge carriers in the film allowing current to more easily flow.
Among the systems receiving attention in this regard are carbon-black organic polymer composites which are deposited by spin or drop coating on interdigitated arrays. Inclusion of the carbon black component into the active sensor material is for the sole purpose of obtaining a measurable DC conductivity through the non-conductive active polymer material. The introduction of analyte material causes polymer swelling and consequent resistance changes of the polymer composite films. To identify specific vapors from a suite of possible substances and to determine the concentration of that vapor or to carry out similar measurements on multi-component systems requires the construction of arrays of sensing elements. Pattern recognition techniques or principal component analysis of the output of an array of sensors can be used for purposes of analyte identification and quantification.
In such systems carbon black acts as a conductive bridge between its atoms. The charge flows more easily when atoms are close together and has more difficulty flowing when the polymer swells and increases the carbon atom separation. Carbon black sensors have differentiated between things as closely related as molecular enantiomers. For example, in one system a chiral polymer was doped with carbon black and then exposed to the + and xe2x88x92 forms of an enantiomeric gas. The gas was absorbed differently between the +/xe2x88x92 case and a 10-20 Ohm difference in the total resistance response was observed between the two molecules (E. Severin et al., Anal. Chem. 70, 1440-1443, (1998)).
However, a number of shortcomings are associated with the use of the carbon-black organic polymer composites. First, it is difficult to reliably reproduce the performance characteristics of a given set of chemiresistor elements due to uncontrollable variations in composite construction. Second, spin coated or drop coated carbon-black polymer composites are inherently metastable in nature and may change or degrade with time. Third, metastable composite systems may not reliably adhere to a substrate surface. Fourth, repeated exposure of the metastable sensor element to analyte vapor may lead to misleading drifts and/or changes in performance characteristics. Fifth, the carbon in a composite material may slowly release analyte material following exposure to analyte and thus have a slow recovery time. Sixth, the interdigitated arrays generally consist of two componentsxe2x80x94a glass substrate and a metallic thin film or wire along with interface regions. Such complicated structures can lead to adhesion problems. Furthermore, carbon-black cannot be used for biological sensing because sensors based on biological molecules and attached to a substrate cannot effectively incorporate a material such as carbon-black.
Accordingly, a need exists for an enhanced microsensor that has improved sensitivity to identifying the presence of and quantifying the concentration of a particular analyte.
The present invention provides a method and apparatus for determining the presence and quantity of biological and/or chemical analytes using a hybrid sensor capable of simultaneous measurement of a volumetric and electrical property of a material responsive to the presence of the particular biological or chemical analyte of interest.
In one embodiment, the hybrid sensor according to the present invention analyzes a sample by simultaneously monitoring the impedance and thickness changes in a sensor material exposed to a sample.
In another embodiment, the sensor material is a lithium perchlorate doped polyethylene oxide thin film.
In still another embodiment, the impedance is measured by a frequency analyzer in signal communication with a sensing material and/or the thickness is measured by a deflectable microcantilever sensor in contact with a surface of the sensing material.
In yet another embodiment, the hybrid sensor is designed to determine both the identity and concentration of a particular analyte in a sample.
In still yet another embodiment, the invention is directed to a hybrid sensor system comprising an array of separate hybrid sensors.
In still yet another embodiment, the invention is directed to a method of constructing a hybrid sensor according to the current invention.
In still yet another embodiment, the invention is directed to a method of determining at least one of the identity and/or concentration of an analyte in a sample using a hybrid sensor as described herein.